title: Leucine-rich glioma inactivated 3 promotes HaCaT keratinocyte migration.
abstract: Our finding that human skin expresses leucine-rich glioma inactivated 3 (LGI3) raises the question of the function of this cytokine in keratinocytes. We have shown that LGI3 stimulates human HaCaT keratinocyte migration without affecting viability or proliferation. Western blot analysis showed that LGI3 induced focal adhesion kinase activation, Akt phosphorylation, and glycogen synthase kinase 3β (GSK3β) phosphorylation in these cells. Using the scratch wound assay and a modified Boyden chamber, we found that LY294002, a selective phosphatidylinositol 3-kinase inhibitor, and LiCl, a selective GSK3β inhibitor, abolished LGI3-induced cell migration. We tested β-catenin levels after LGI3 treatment because the Akt-GSK3β pathway regulates β-catenin accumulation, and β-catenin promotes cell migration. LGI3 treatment increased β-catenin protein and nuclear localization, whereas LY294002 prevented LGI3-induced focal adhesion kinase and Akt activation as well as β-catenin accumulation. Overall, these data suggest that LGI3 stimulates HaCaT cell migration following β-catenin accumulation through the Akt pathway.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Jeong
authors.forename: Woo-Jae
authors.initials: WJ
authors.lastname: Park
authors.forename: Myo-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000378:metabolism; D051176:beta Catenin / Q000187:drug effects / Q000378:metabolism
chemical_list: C456924:LGI3 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D051176:beta Catenin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3